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An Open-label Study of Hydromorphone Oral Solution in Subjects Aged 28 Days to 16 Years for Postoperative PainRecruiting

The primary objective of this study is to characterize the pharmacokinetics and
pharmacodynamics of hydromorphone oral solution in pediatric subjects aged 28 days to 16
years inclusive. The secondary objectives are to characterize the safety and efficacy of
hydromorphone oral solution in pediatric subjects aged 28 days to 16 years inclusive.

Abstract

The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and to improve patient outcomes.2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock.Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001-2006).The Pubmed/MEDLINE literature database (1966-2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus.The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%-3% in previously healthy, and 7%-10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained.The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill 70% and cardiac index 3.3-6.0 L/min/m.

Abstract

Control of hyperglycemia in adult medical and surgical intensive care units (ICUs) has been shown to dramatically decrease morbidity and mortality. Algorithms to achieve glycemic control in the ICU setting are evolving. We have evaluated the use of a discrete proportional-integral-derivative (PID) algorithm to control hyperglycemia in pediatric ICU (PICU) patients both with and without diabetes.Six PICU patients [four with diabetic ketoacidosis (DKA) and two with glucocorticoid-induced hyperglycemia] with glucose values >150 mg/dL were enrolled. Their hyperglycemia was managed with a PID algorithm that provided recommendations for both changes in the intravenous insulin infusion rate and the time to obtain the next discrete glucose value. Glucose targets were adjusted based on clinical circumstances.Patients (mean age 9.2 years; range 1.8-14 years) utilized the algorithm for a total of 454.4 h. Mean time to the initial glucose target was 8.7 h (range 1.3-15.1 h) in five patients. One subject with hyperosmolar DKA did not achieve target before discharge from the PICU, and another was at target when the algorithm was initiated. After the glucose target was achieved, the mean SD was 23.5 mg/dL, and glucose values were >40 mg/dL above target 13% of the time and <40 mg/dL below target 1% of the time. There were no glucose values <55 mg/dL.The PID algorithm safely and effectively controlled hyperglycemia in a PICU, despite multiple changes in intravenous fluids, steroid doses (including high-dose pulses), and hemodialysis.

Abstract

We evaluated retrospectively plasma glucose levels and the degree of hypoglycemia, hyperglycemia, and glucose variability in a PICU and then assessed their association with hospital length of stay and mortality rates.Electronic medical records at the Packard Children's Hospital at Stanford University were reviewed retrospectively for all PICU admissions between March 1, 2003, and March 31, 2004. Patients with a known diagnosis of diabetes mellitus were excluded. The prevalence of hyperglycemia was defined with cutoff values of 110, 150, and 200 mg/dL. Hypoglycemia was defined as < or = 65 mg/dL. Glucose variability was assessed with a calculated glucose variability index.In 13 months, 1094 eligible admissions generated 18865 glucose values (median: 107 mg/dL; range: 13-1839 mg/dL). Patients in the highest maximal glucose quintile had a significantly longer median PICU length of stay, compared with those in the lowest quintile (7.5 days vs 1 day). Mortality rates increased as patients' maximal glucose levels increased, reaching 15.2% among patients with the greatest degree of hyperglycemia. Hypoglycemia was also prevalent, with 18.6% of patients (182 of 980 patients) having minimal glucose levels of < or = 65 mg/dL. There was an increased median PICU length of stay (9.5 days vs 1 day) associated with glucose values in the lowest minimal quintile, compared with those in the highest quintile. Hypoglycemia was correlated with mortality rates; 16.5% of patients with glucose levels of < or = 65 mg/dL died. Glucose variability also was associated with increased length of stay and mortality rates. In multivariate logistic regression analyses, glucose variability, taken with hyperglycemia and hypoglycemia, showed the strongest association with mortality rates.Hyperglycemia and hypoglycemia were prevalent in the PICU. Hypoglycemia, hyperglycemia, and, in particular, increased glucose variability were associated with increased morbidity (length of stay) and mortality rates.

Abstract

Past literature has shown that respiratory failure following hematopoietic stem cell transplant is associated with a universally poor outcome with mortality rates approaching 100%. More recent studies have suggested that patient survival is improving. We report our experience with the patients from our institution, a large children's hospital, who were admitted to the intensive care unit (ICU). Medical records of 183 patients, who received a bone marrow transplant between 1992 and early 2004, who were <20 yr of age, were retrospectively reviewed. Various factors that might influence mortality were examined. Over the course of the study, the ICU survival increased from 18% during the period 1992-1999 to 59% between 2000 and early 2004. In the latter period, 54% of the patients discharged from the ICU were alive at 100 days post-transplant. Factors that were significant predictors of poor outcome were malignancy as the reason for transplant, dialysis during the ICU stay, or extreme respiratory failure with a ratio of arterial oxygen tension (PaO2)/inspired oxygen concentration (FiO2) <300. Analysis of patients who required a high positive end-expiratory pressure or were ventilated with permissive hypercapnia showed that they also had a higher mortality. The impact on survival of factors such as age at time of transplant, graft-vs.-host disease, pneumonia, bacteremia, sepsis, post-transplant days, Pediatric Risk of Mortality III score, engraftment status, or veno-occlusive disease did not reach statistical significance in this cohort. Survival has improved for children who require intensive care following a bone marrow transplant, even for those who require mechanical ventilation. Patients with extreme respiratory failure and those requiring dialysis continue to have poor outcome. Because of an overall improvement in survival, children whose condition following transplant requires intensive care should be treated aggressively.